Visualizing lysosomes hypochlorous acid in Parkinson's disease models by a novel fluorescent probe.

ABSTRACT

Heightened oxidative stress is the principal driver behind the altered metabolism of neurotransmitters within the brains of Parkinson's disease (PD). Hypochlorous acid (HClO), a variant of reactive oxygen species (ROS), plays a crucial role in several lysosomal activities. An irregular concentration of HClO may result in significant molecular damage and contribute to the onset of neurodegenerative disorders. Despite this, the precise role of lysosomal HClO in PD remains unclear, due to its fast reactivity and low levels. This is further complicated by the lack of effective in situ imaging techniques for accurately tracking its dynamics. Therefore, it is of great significance to use effective tools to map the lysosomal HClO during the pathological process of PD. In this study, we propose a fluorogenic probe named Lys-PTZ-HClO for the specific and sensitive detection of HClO. Lys-PTZ-HClO exhibits features like a fast response time (10 s) and a low detection limit (0.72 µM). Benefiting from its superior properties, the probe was used to visualize the basal HClO levels, and the variation of HClO levels in lysosomal of living cells. More importantly, this probe was successfully applied for the first time to reveal increased lysosomal HClO in a cellular model of PD.